Yohimbine is often perceived as a 'light' herbal ingredient of fat burners. However, in pharmacology it is a potent blocker of alpha-2-adrenergic receptors, and toxicology centers regularly receive calls related to it. Fatal cases have also been described. The editorial team examined how to recognize an overdose, why it occurs even without a deliberate exceeding of the dose, and what to do if symptoms have already appeared.
Why yohimbine is easy to overdose on
The first cause is the mechanism of action. Yohimbine blocks presynaptic alpha-2-adrenergic receptors, which normally restrain the release of norepinephrine. When this 'brake' is switched off, the sympathetic nervous system works more intensively: the pulse, blood pressure and level of anxiety rise. There is a small distance here between the desired effect and the toxic one.
The second cause is unpredictable pharmacokinetics. The study by Owen and colleagues (1987) showed that yohimbine is eliminated quickly, but its bioavailability when taken orally varies within very wide limits between different people. That is, the same tablet will give almost no effect in one person and create a high blood concentration in another.
Part of this variability is explained by genetics. Yohimbine is metabolized in the liver mainly by the enzyme CYP2D6, whose activity varies genetically. The work of Le Corre and colleagues (2004) demonstrated that in people with low activity of this enzyme the sympathetic reaction to yohimbine is much more pronounced.
The third cause is the quality of supplements. The study by Cohen and colleagues (2016) showed that the actual yohimbine content in products on the US market often did not match the label, and some contained pharmaceutical quantities of the alkaloid. Added to this are other stimulants in the composition of the same products, which enhance the total effect.
Signs of overdose
The picture of a yohimbine overdose is a picture of excessive sympathetic stimulation. It usually develops within the first hour after intake. A person feels a strong heartbeat, internal trembling, restlessness, fear, which can turn into panic.
The analysis by Kearney, Tu and Haller (2010), which covered calls to the California poison control system, showed that the most frequent manifestations were tachycardia, gastrointestinal disorders, anxiety and agitation, as well as a rise in blood pressure. Some patients required hospitalization.
In addition, characteristic are reddening of the skin, sweating, chills, nausea and vomiting, headache, frequent urination. In men priapism is possible - a prolonged painful erection that requires emergency urological help.
| System | Mild manifestations | Severe manifestations |
|---|---|---|
| Cardiovascular | Heartbeat, moderate rise in blood pressure | Hypertensive crisis, arrhythmias, chest pain |
| Nervous | Anxiety, tremor, insomnia | Panic attack, confusion, seizures |
| Digestive | Nausea, discomfort in the abdomen | Repeated vomiting, dehydration |
| Skin, thermoregulation | Reddening, sweating | Hyperthermia |
| Genitourinary | Frequent urination | Priapism |
Important: mild manifestations can escalate quickly, especially if the person has simultaneously consumed caffeine, other stimulants or alcohol, or is training in the heat. Therefore even 'ordinary' anxiety with heart palpitations after a new fat burner is a signal to stop intake and monitor the condition.
Severe complications and fatal cases
In the medical literature, cases have been described in which taking yohimbine led to serious neurological and cardiovascular complications. Giampreti and colleagues (2009) reported acute neurotoxicity in a bodybuilder after consuming yohimbine, with seizures and prolonged impairment of consciousness that required intensive care.
Anderson and colleagues (2013) described two fatal cases of acute yohimbine intoxication, confirmed by toxicological analysis. These reports are important because they prove that death from yohimbine is not a theoretical risk but a documented fact.
The review by Cimolai and Cimolai (2011), devoted to the use of yohimbine for 'physical enhancement', summarized cases of hypertensive crises, arrhythmias, seizures and acute organ damage. The authors emphasized that toxic effects arose at doses that consumers considered acceptable.
The mechanisms of severe complications are associated with a sharp rise in blood pressure (risk of cerebral hemorrhage, aortic dissection), heart rhythm disturbances, seizures and hyperthermia with subsequent rhabdomyolysis and kidney damage. Each of these complications can be life-threatening.
Who is at increased risk
Some people react to yohimbine much more strongly than others. For example, the study by Charney and colleagues (1984) showed that in people with panic disorder yohimbine easily provokes panic attacks. For them even a small amount of the substance can cause a pronounced reaction.
Separately worth highlighting are people with reduced CYP2D6 activity and those who take drugs that inhibit this enzyme (in particular some antidepressants). The concentration of yohimbine in them can be many times higher than expected.
- people with arterial hypertension, heart diseases, arrhythmias;
- patients with anxiety disorders, panic disorder, bipolar disorder;
- people with kidney and liver diseases;
- those who take antidepressants, stimulants, drugs for ADHD;
- pregnant and breastfeeding women;
- athletes who combine yohimbine with caffeine and other fat burners against the background of dieting and dehydration.
The package insert for prescription yohimbine hydrochloride in the USA directly indicated that the drug is not intended for use in patients with kidney diseases, mental disorders, or together with agents that affect mood. These warnings remain relevant for products sold as supplements.
What to do if an overdose is suspected
If after taking a product with yohimbine a strong heartbeat, chest pain, a sharp headache, confusion, seizures or a very high temperature appear, you need to call an ambulance immediately. This is not a case where it is worth 'waiting it out'.
Before the medics arrive, the person should be laid down in a cool place, provided with access to air, and not given any stimulants, coffee or energy drinks. It is important to keep the product's packaging: information about the composition will help the doctors. You should not try to 'neutralize' the condition with other drugs on your own.
In the hospital, treatment is mostly supportive: monitoring of the ECG and blood pressure, infusion therapy, sedatives (usually benzodiazepines) for agitation and seizures, cooling for hyperthermia. The literature also discusses the use of clonidine - an agonist of alpha-2 receptors that acts opposite to yohimbine. The choice of drugs remains with the doctor.
After an overdose episode it is advisable to check kidney function, creatine kinase and electrolytes, and to completely give up products with yohimbine. A repeated reaction in the same person will most often be no less pronounced.
Editorial conclusions
Yohimbine has a narrow margin between action and toxicity, and its blood concentration varies greatly between people because of variable bioavailability and the genetics of the CYP2D6 enzyme.
An overdose manifests with tachycardia, a rise in blood pressure, anxiety, nausea and tremor, and in severe cases - seizures, arrhythmias and hyperthermia. Fatal cases have been described.
The mismatch between the composition of supplements and the label, and the combination with other stimulants, make an 'ordinary' dose unpredictable, so the best prevention is refusing uncontrolled consumption.
We also recommend reading our articles on the interaction of yohimbine with other drugs, on the effect of yohimbine on the liver and kidneys, and on the history of yohimbine from the laboratory to sport.
References
- Kearney T, Tu N, Haller C. Adverse drug events associated with yohimbine-containing products: a retrospective review of the California Poison Control System reported cases. Ann Pharmacother. 2010;44(6):1022–1029.
- Anderson C, Anderson D, Harre N, Wade N. Case study: two fatal case reports of acute yohimbine intoxication. J Anal Toxicol. 2013;37(8):611–614.
- Giampreti A, Lonati D, Locatelli C, et al. Acute neurotoxicity after yohimbine ingestion by a body builder. Clin Toxicol (Phila). 2009.
- Cimolai N, Cimolai T. Yohimbine use for physical enhancement and its potential toxicity. J Diet Suppl. 2011;8(4):346–354.
- Owen JA, Nakatsu SL, Fenemore J, et al. The pharmacokinetics of yohimbine in man. Eur J Clin Pharmacol. 1987;32(6):577–582.
- Le Corre P, Parmer RJ, Kailasam MT, et al. Human sympathetic activation by alpha2-adrenergic blockade with yohimbine: bimodal, epistatic influence of cytochrome P450-mediated drug metabolism. Clin Pharmacol Ther. 2004;76(2):139–153.
- Cohen PA, Wang YH, Maller G, et al. Pharmaceutical quantities of yohimbine found in dietary supplements in the USA. Drug Test Anal. 2016;8(3-4):357–369.
- Charney DS, Heninger GR, Breier A. Noradrenergic function in panic anxiety: effects of yohimbine in healthy subjects and patients with agoraphobia and panic disorder. Arch Gen Psychiatry. 1984;41(8):751–763.
Andriy Melnyk
A strength-sports coach and author of programs for beginner and intermediate levels. Writes about training planning.
